The following discussion of the prior art is intended to present the invention in an appropriate technical context and allow its significance to be properly appreciated. Unless clearly indicated to the contrary, however, reference to any prior art in this specification should be construed as an admission that such art is widely known or forms part of common general knowledge in the field.
FARXIGA® is a sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The active ingredient of the approved product FARXIGA Dapagliflozin, which is described chemically as D-glucitol, 1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-,(1S)-, compounded with (2S)-1,2-propanediol, hydrate (1:1:1). The empirical formula is C21H25ClO6.C3H8O2.H2O and the molecular weight is 502.98. The structural formula is:

U.S. Pat. No. 6,515,117 discloses the compound dapagliflozin and a process for its preparation wherein dapagliflozin is obtained as glassy off-white solid having 94% purity and containing 0.11 mol % of EtOAc.
U.S. Pat. No. 7,919,598, U.S. PG-Pub. No. 2013/0303467 and International (PCT) Publication No. WO 2013/079501 discloses various crystalline forms of dapagliflozin viz. hydrates, anhydrous forms, solvates and complexes with amines and amino acids.
U.S. Pat. No. 8,999,941 discloses a process for preparation of amorphous dapagliflozin comprising adding a heated solution of dapagliflozin in toluene into n-heptane. After drying in vacuo the product was obtained as a white solid with melting point of 49.5° C. to 62.6° C. DSC analysis showed the existence of two endothermic transitions at 57° C. and 107° C. which were indicative of dehydration and solvent evaporation. The prior art fails to describe the purity and level of the residual solvents in final product.
International (PCT) Publication No. WO 2015/011113 discloses an amorphous solid dispersion of dapagliflozin and a polymer as well as process for its preparation.
International (PCT) Publication No. WO 2015/104658 discloses a process for the preparation of an amorphous form of dapagliflozin by dissolving dapagliflozin in solvents and removing the solvent. Also disclosed is an amorphous solid dispersion of dapagliflozin together with one or more pharmaceutically acceptable carriers as well as process for its preparation.
International (PCT) Publication No. WO 2015/128853 discloses a pharmaceutical composition comprising a solid dispersion of dapagliflozin and one or more pharmaceutically acceptable excipients and process for the preparation thereof.
International (PCT) Publication No. WO 2015/132803 discloses crystalline glycerol solvate of dapagliflozin and process for its preparation by treating dapagliflozin with glycerol in water.
International (PCT) Publication No. WO 2015/117538 discloses new dapagliflozin crystalline form with absorption peak at about 4.318(20.45) in X-ray powder diffraction pattern shown by angle 28 and inter planar spacing (value d) and process for its preparation.
Solvates and hydrates can be very stable solid forms and may have definite benefits in regard to manufacturing. Stable polymorphic forms of dapagliflozin can be crystallized as solvates of the present invention.
Crystalline solids normally require a significant amount of energy for dissolution due to their highly organized, lattice like structures. For example, the energy required for a drug molecule to escape from a crystal is more than from an amorphous or a non-crystalline form. It is known that the amorphous forms in a number of drugs exhibit different dissolution characteristics and in some cases different bioavailability patterns compared to the crystalline form (Econno T., Chem. Pharm. Bull., 1990; 38: 2003-2007). For some therapeutic indications, one bioavailability pattern may be favoured over another.
An amorphous form of some of the drugs exhibit much higher bioavailability than the crystalline forms, which leads to the selection of the amorphous form as the final drug substance for pharmaceutical dosage from development. Additionally, the aqueous solubility of crystalline form is lower than its amorphous form in some of the drugs, which may have resulted in the difference in their in-vivo bioavailability. Therefore, it is desirable to have amorphous forms of drugs with high purity to meet the needs of regulatory agencies and also highly reproducible processes for their preparation.
As discussed herein above, the current art processes provides an amorphous dapagliflozin with low purity and high residual solvents which is not suitable for pharmaceutical preparations. Therefore, there still exists a need to provide an efficient process for preparation of an amorphous dapagliflozin that provides dapagliflozin with higher purity and lower levels of residual solvent(s) in accordance with the ICH guidelines which is suitable for pharmaceutical preparations.